Carvacryl Acetate Research Articles

In silico Screening of Plectranthus amboinicus and Hyptis suaveolens Phyto-chemicals: Novel Repellents Targeting Odorant Binding Proteins of Aedes aegypti and Aedes albopictus

Background and Aim: Mosquitoes significantly threaten public health, transmitting dangerous diseases to humans and animals. Conventional insecticide spraying, while common, has limitations in effectively controlling vector-borne diseases. Many chemical pesticides harm humans and animals, and some persist in the environment and cause toxic effects. Recently, there has been renewed interest in plant-based products due to concerns about insecticide re-sistance, cross-resistance, potential toxicity associated with synthetic options, and rising costs. Therefore, this study aimed to screen the Plectranthus amboinicus and Hyptis suaveolens phy-tochemicals targeting the odorant binding proteins (OBPs) of Aedes aegypti and Aedes albopic-tus. Methods: In this study, we conducted molecular docking analyses using specific plant-derived compounds from H. suaveolens and P. amboinicus. Results: We focused on the interaction of these compounds with OBPs from dengue and chikungunya vectors (Aedes aegypti and Aedes albopictus). The selected phytochemical com-pounds exhibited strong binding with the OBP of both Ae. aegypti and Ae. albopictus. Tetrahy-drofuran-2-carboxylic acid, Carvacryl acetate, and Brallobarbital showed high binding affinity and significant interaction with Ae. aegypti. Tetrahydrofuran-2-carboxylic acid and 3-Methyl-4-isopropylphenol also demonstrated substantial binding affinity and effective interaction with Ae. albopictus OBP. Conclusion: These findings suggest that the identified compounds can potentially disrupt the attraction of mosquitoes to humans, thus reducing human-vector contact. They may offer a promising alternative for developing natural and efficient mosquito repellents, surpassing cur-rently used synthetic options like N, N-diethyl-meta-toluamide, and other conventional repel-lents.

Aceite esencial de hojas de Minthostachys mollis[HBK] Griseb. del Ecuador: Extracción, composición química, capacidad antioxidante y actividad antimicrobiana

The aim of this study was to optimize by response surface design, the extraction of the leafessential oil (EO) from Minthostachys mollis [HBK] Griseb., grown in Ecuador, using steam distillation. The factors used were extraction time (XTIE) of 60, 105 and 150 min and plant material/water ratio (XRMA) of 1:3, 1:4 and 1:5. The optimal combination was reached with XRMA 1:5 and XTIE 150 min, obtaining a process yield of 0.67%. The chemical composition of the EO analyzed by GC-MS was determined, where the main compounds were carvacryl acetate (44.01%), carvacrol (16.51%) and menthone (8.20%). The antioxidant capacity of EO was evaluated using the FRAP and ABTS methodologies, with an IC50243.21 μmol Fe2+/g and 0.12 mg/mL, respectively. In addition, the antimicrobial activity of EO was found against Pseudomonas aeruginosa, Salmonella enterica, Escherichia coliand Staphylococcus aureus.

Effect of the Combination of Synthetic Anthelmintics with Carvacryl Acetate in Emulsions with and without a Sodium Alginate Matrix on Haemonchus contortus.

The present study aimed to evaluate the effect of nanoemulsions using combined synthetic anthelmintics, thiabendazole (TBZ), levamisole (LEV), and ivermectin (IVM), with carvacryl acetate (CA) against Haemonchus contortus, and also tested the presence and absence of alginate (ALG). The anthelmintic effect of the CA/TBZ nanoemulsion was evaluated in the egg hatch test (EHT). The effects of CA/IVM and CA/LEV nanoemulsions were evaluated in the larval development test (LDT). The emulsions CA/TBZ/ALG and CA/TBZ showed a multimodal profile, with most particles on the nanometric scale. The encapsulation efficiency in CA/TBZ/ALG was 80.25%, and that in CA/LEV/ALG was 89.73%. In the EHT, CA/TBZ and CA/TBZ/ALG showed mean combination indices (CIs) of 0.55 and 0.36, respectively, demonstrating synergism in both. In LDT, CA/IVM had an average CI of 0.75, and CA/LEV and CA/LEV/ALG showed CI values of 0.4 and 0.93, respectively. It was concluded that CA/TBZ showed a synergistic interaction, and CA/TBZ/ALG showed an enhanced effect. In addition, the matrix brought stability to the product, encouraging its improvement to obtain higher efficacy.

Nanoemulsion Improves the Anti-Inflammatory Effect of Intraperitoneal and Oral Administration of Carvacryl Acetate.

Carvacryl acetate (CA) is a monoterpene obtained from carvacrol, which exhibits anti-inflammatory activity. However, its low solubility in aqueous media limits its application and bioavailability. Herein, we aimed to develop a carvacryl acetate nanoemulsion (CANE) and assess its anti-inflammatory potential in preclinical trials. The optimized nanoemulsion was produced by ultrasound, and stability parameters were characterized for 90 days using dynamic light scattering after hydrophilic-lipophilic balance (HLB) assessment. To evaluate anti-inflammatory activity, a complete Freund's adjuvant-induced inflammation model was established. Paw edema was measured, and local interleukin (IL)-1β levels were quantified using ELISA. Toxicity was assessed based on behavioral changes and biochemical assays. The optimized nanoemulsion contained 3% CA, 9% surfactants (HLB 9), and 88% water and exhibited good stability over 90 days, with no signs of toxicity. The release study revealed that CANE followed zero-order kinetics. Dose-response curves for CA were generated for intraperitoneal and oral administration, demonstrating anti-inflammatory effects by both routes; however, efficacy was lower when administered orally. Furthermore, CANE showed improved anti-inflammatory activity when compared with free oil, particularly when administered orally. Moreover, daily treatment with CANE did not induce behavioral or biochemical alterations. Overall, these findings indicate that nanoemulsification can enhance the anti-inflammatory properties of CA by oral administration.

Docking Studies of Natural Product Derived Carvacrol Type Aromatic Monoterpenes Against COVID-19 and Comparison with Used Synthetic Drugs: Potential of Carvacryl Acetate Against SARS-CoV-2 (COVID-19)

The COVID-19 pandemic that broken out in 2020 is becoming more worrying for the world. Although there is no 100 % success against COVID-19, certain synthetic drugs are currently used despite various side effects. Therefore, studies on the discovery of new treatment alternatives come to the fore. Studies so far show that natural products are still important resources for the discovery of new therapeutic agents. Plant-derived essential oils are complex volatiles composed of various phytochemicals, mostly containing compounds such as sesquiterpenes, monoterpenes, and phenylpropanoids. In this study, especially thymol and carvacrol compounds specific to the Lamiaceae (Labiate) family and aromatic monoterpenes derived from these compounds were modeled against COVID-19. Results were compared with remdesivir, hydroxychloroquine, and favipiravir used as synthetic drugs. Dock and molecular dynamics simulations analyzed these molecules’ potential inhibitor efficiency of the SARS-CoV2 Mpro. Lipinski parameters and Docking results were demonstrated that ligands carvacrol (2), carvacryl acetate (11) and cuminaldehyde (12) are potential inhibitors towards COVID-19. According to the results, it is seen that medicinal aromatic herbs, which contain these volatile components with the fewer side effects than synthetic drugs, have the potential to be used as supplements in the pharmaceutical industry.

Enhancing the antischistosomal activity of carvacryl acetate using nanoemulsion.

Aim: To formulate a carvacryl acetate nanoemulsion (CANE) and test its antischistosomal activity. Materials & methods: CANE was prepared and tested in vitro on Schistosoma mansoni adult worms and both human and animal cell lines. Next, CANE was administered orally to mice infected with either a prepatent infection or a patent infection of S. mansoni. Results: CANE was stable during 90 days of analysis. CANE showed in vitro anthelmintic activity, and no cytotoxic effects were observed. In vivo, CANE was more effective than the free compounds in reducing worm burden and egg production. Treatment with CANE was more effective for prepatent infections than praziquantel. Conclusion: CANE improves antiparasitic properties and may be a promising delivery system for schistosomiasis treatment.

Chemotypes and Their Stability in Mentha longifolia (L.) L.-A Comprehensive Study of Five Accessions.

Mentha longifolia (L.) L. is the most widespread wild-growing mint species found, and its chemical composition is extremely diverse. We studied the essential oil (EO) yield, composition, and chemotaxonomy of five, northern Hungarian accessions of the species in a cultivation experiment covering two vegetation years at two parallel sites. The long-term goal is to establish the cultivation of this stress-tolerant species in Hungary as a source of flavoring and preservative agents for commercial use. Essential oil yield (1–2 mL/100 g) was observed to be dependent on both the accession and the year. Accession HV1 is assumed to be a new, presumably rare chemotype containing carvacrol (19.28–20.56%), 1,8-cineole (14.87–17.45%), thymol (13.36–13.90%), carvacryl acetate (8.81–10.40%), and para-cymene (7.24–8.01%). Only minor fluctuations occurred in concentrations of these constituents due to habitats and years. A radical change in essential oil composition was observed in accession HV2, as one batch was based on thymol (19.79%) and 1,8-cineole (14.93%), while the others were rich in dihydrocarvone isomers (up to 69%). Although this needs further investigation, it does explain the coexistence of limonene-oxo and γ-terpinene pathways in horsemint. According to the literature, the pathway leading to thymol isomers and/or esters may be rare in the entire Mentha genus. We also demonstrated that known chemotypes of horsemint may differ in variability of their EO composition. Our results also led to the conclusion that any declaration on chemotype needs detailed examination and is not realistic on the basis of a single sample. Assumptions were made about the potential areas of utilization: beside fragrance and flavoring uses of essential oils free from pulegone and menthofurane, thymol-based ones may be used as antioxidative and anti-spoilage agents.

Efficacy of carvacryl acetate in vitro and following oral administration to mice harboring either prepatent or patent Schistosoma mansoni infections.

Schistosomiasis is a major public health problem that afflicts more than 240 million individuals globally, particularly in poor communities. Treatment of schistosomiasis relies heavily on a single oral drug, praziquantel, and there is interest in the search for new antischistosomal drugs. This study reports the anthelmintic evaluation of carvacryl acetate, a derivative of the terpene carvacrol, against Schistosoma mansoni ex vivo and in a schistosomiasis animal model harboring either adult (patent infection) or juvenile (prepatent infection) parasites. For comparison, data obtained with gold standard antischistosomal drug praziquantel are also presented. Initially in vitro effective concentrations of 50% (EC50) and 90% (EC90) were determined against larval and adult stages of S. mansoni. In an animal with patent infection, a single oral dose of carvacryl acetate (100, 200, or 400mg/kg) caused a significant reduction in worm burden (30-40%). S. mansoni egg production, a process responsible for both life cycle and pathogenesis, was also markedly reduced (70-80%). Similar to praziquantel, carvacryl acetate 400mg/kg had low efficacy in pre-patent infection. In tandem, although carvacryl acetate had interesting in vitro schistosomicidal activity, the compound exhibited low efficacy in terms of reduction of worm load in S. mansoni-infected mice.

Carvacryl acetate nanoencapsulated with chitosan/chichá gum exhibits reduced toxicity in mice and decreases the fecal egg count of sheep infected with gastrointestinal nematodes.

The nanoencapsulation of biocomposites with anthelmintic action has been proposed as an alternative for improving their efficiency. Thus, the current study aimed to evaluate the efficacy of carvacryl acetate nanoencapsulated with biopolymers (nCVA) in the control of sheep gastrointestinal nematodes. CVA was nanoencapsulated with chitosan/chichá gum and characterized in terms of its efficacy of encapsulation (EE), yield and zeta potential. The acute toxicity of nCVA was evaluated in mice. For the fecal egg count reduction test, 40 animals were divided into four groups (n = 10) and orally administered the following treatments: G1, 250 mg kg−1 CVA; G2, 250 mg kg−1 nCVA; G3, chitosan/chichá gum (negative control) and G4, 2.5 mg kg−1 monepantel (positive control). Feces were collected on days 0 and 16 posttreatment to determine the eggs per gram of feces (epg). The EE and yield of nCVA were 72.8 and 57.5%, respectively. The nanoparticles showed a size of 764.5 ± 302.5 nm, and the zeta potential at pH 3.2 was +22.0 mV. nCVA presented a 50% lethal dose (LD50) of 2609 mg kg−1. By 16 days posttreatment, CVA, nCVA and monepantel reduced the epg by 52.9.7, 71.5 and 98.7%, respectively, and the epg of sheep treated with nCVA differed from that of the negative control (P > 0.05) but did not differ from that of sheep treated with CVA. In conclusion, the nanoencapsulation of CVA reduced its toxicity, and nCVA showed anthelmintic activity.

Erratum: Anthelmintic activity of nanoencapsulated carvacryl acetate against gastrointestinal nematodes of sheep and its toxicity in rodents.

[This corrects the article doi: 10.1590/s1984-29612019098].

Anthelmintic activity of nanoencapsulated carvacryl acetate against gastrointestinal nematodes of sheep and its toxicity in rodents.

The objective of this study was to evaluate the efficacy of carvacryl acetate (CVA) and nanoencapsulated CVA (nCVA) on gastrointestinal nematodes of sheep. The CVA was nanoencapsulated with chitosan/gum arabic and the efficacy of nanoencapsulation (EE), yield, zeta potential, nanoparticle morphology and release kinetics at pH 3 and 8 were analyzed. Acute and subchronic toxicity were evaluated in rodents and reduction of egg counts in the faeces (FECRT) of sheep. The sheep were divided into four groups (n = 10): G1, 250 mg/kg CVA; G2, 250 mg/kg nCVA; G3, polymer matrix and G4: 2.5 mg/kg monepantel. EE and nCVA yield were 65% and 57%, respectively. The morphology of the nanoparticles was spherical, size (810.6±286.7 nm), zeta potential in pH 3.2 (+18.3 mV) and the 50% release of CVA at pHs 3 and 8 occurred at 200 and 10 h, respectively. nCVA showed LD50 of 2,609 mg/kg. CVA, nCVA and monepantel reduced the number of eggs per gram of faeces (epg) by 57.7%, 51.1% and 97.7%, respectively. The epg of sheep treated with CVA and nCVA did not differ from the negative control (P>0.05). Nanoencapsulation reduced the toxicity of CVA; however, nCVA and CVA presented similar results in the FECRT.

Chitosan Nanoparticles Loaded with Carvacrol and Carvacryl Acetate for Improved Anthelmintic Activity

Carvacrol (CV) and carvacryl acetate (CVA) are bioactive compounds that have anthelmintic action and the nanoencapsulation may be an alternative to potentialize their efficacy. The aim of this work was to nanoencapsulate CV and CVA using chitosan/gums and evaluate cytotoxicity and the anthelmintic activity. A 24 factorial experimental design was performed to determine the influence of gum type (arabic or chicha), amount of surfactant and the number of layers in the nanoencapsulation degree. CVA and CV presented encapsulation efficiency (EE) optimum values of 90 and 20% (experiments 8 and 9), respectively. The monolayer and bilayer formulations presented maximum size of 479 and 811 nm, respectively. Nanoencapsulated CVA (nCVA) with bilayer coating and higher surfactant levels showed good thermal stability and no toxicity. In vitro kinetics for nCVA with chitosan/chicha gum showed slower release profiles than nCVA with chitosan/gum arabic, with 50% release after 30 and 20 h, respectively. CVA and nCVA at a concentration of 150 µg mL−1 reduced the motility of H. contortus adult nematodes by 100 and 91.7%, respectively. In summary, nCVA chitosan/chicha gum showed high encapsulation efficiency, favorable release rate and anthelmintic activity against H. contortus.

Acetato de Carvacrila: Síntese e Atividades Toxicológicas e Farmacológicas

In this work, we report a synthetic route to carvacryl acetate. In addition to the chemical synthesis, this study aimed to evaluate the acute toxicity after administration of carvacryl acetate at doses of 1000 and 2000 mg/kg in male and female Swiss mice treated orally and intraperitoneally. Carvacryl acetate was aseptically suspended in 0.05% Tween 80, dissolved in 0.9% saline (vehicle) and administered orally (p.o.) and intraperitoneally (i.p.) (0, 1000 and 2000 mg/kg). In addition to the acute toxicity, the present study evaluated the antioxidant capacity by inhibition of oxidative hemolysis and using DPPH•, ABTS•+ and by reducing potential. Signs of toxicity and mortality were observed in animals of both sexes after intraperitoneal administration of carvacryl acetate (2000 mg/kg). Additionally, no significant difference in body weight, water intake, food consumption and excreta production of treated animals were detected in comparison with control group (vehicle). In vitro study demonstrated antioxidant capacity using DPPH• (EC50 = 6.1 ± 0.53 µg/ml), ABTS•+ (EC50=5.24 ± 0,38 µg/ml), reducing potential (EC50=3.65 µg/ml) and by inhibition of oxidative hemolysis induced by hydrogen peroxide (EC50= 2.58 ± 0,07 µg/ml). In summary, this study indicated that treatment with carvacryl acetate in selected doses was well tolerated in all animals.

Carvacryl acetate, a semisynthetic monoterpenic ester obtained from essential oils, provides neuroprotection against cerebral ischemia reperfusion-induced oxidative stress injury via the Nrf2 signalling pathway.

Carvacryl acetate (CA) is a semisynthetic monoterpenic ester obtained from essential oils, and it exerts an antioxidation effect. The purpose of our study was to investigate whether CA could provide neuroprotection against oxidative stress caused by cerebral ischemia-reperfusion injury (CIRI) and elucidate the underlying mechanism. Middle cerebral artery occlusion (MCAO)-induced damage was established in Sprague Dawley (SD) rats and PC12 cells were exposed to hydrogen peroxide (H2O2) to imitate oxidative stress damage. TTC, HE and Nissl staining were used to observe the pathological morphology of lesions. The contents of ROS and MDA, and the activity of SOD were measured to reflect the level of oxidative stress. In addition, the TUNEL method was used to assess injuries in vitro, and the expression of Nrf2 was determined by immunohistochemical staining and western blot analysis. Importantly, we constructed and validated Nrf2 knockdown PC12 cells to confirm the key role of Nrf2 in the neuroprotective effect of CA against oxidative stress injuries. CA alleviated CIRI in rats with MCAO, as shown by brain tissue pathophysiology. The contents of ROS and MDA were reduced, and the SOD activity was augmented by the simultaneous promotion of Nrf2 expression. In addition, the H2O2-induced injury in Nrf2-knockdown PC12 cells was more serious than it was in control cells, and CA-mediated neuroprotection was exclusively inhibited by the knock down of Nrf2 in PC12 cells. In conclusion, it is shown here that CA has the effect of relieving cerebral ischemia reperfusion-induced oxidative stress injury via the Nrf2 signalling pathway.

Volatiles from Carissa carandas fruits damaged by conspecifics attract chafer beetles, Protaetia alboguttata (Vigors)

The present study highlights the importance of herbivore induced plant volatiles (HIPVs) in attracting the cetoniid beetles, Protaetia alboguttata (Vigors) to ripe conspecific damaged Carissa carandas L.fruits. Olfactometer assays revealed that volatiles from damaged fruits are significantly attractive to the adult beetles of P. alboguttata. Gas chromatography electroantenno-detection studies revealed that presence of α-copaene and carvacryl acetate in the damaged C. carandas fruits that might be involved in guiding the adult P. alboguttata beetles to their host plants.

Essential oil of Minthostachys mollis: extraction and chemical composition of fresh and stored samples

The objective of this research work was to determine the amount of essential oil obtained from the plant species Mintostachys mollis , using the method of extraction of water-steam distillation by the cohobation process and the comparison of the chemical composition of the fresh and stored samples of the plant. Two factors were experimentally taken into account for the extraction: humidity of the material and time measured in three levels, according to the response variable, which is referred to the volume of extracted oil. The characterization was carried out by gas chromatography/ mass spectrometer. The extraction process showed that the highest yields of essential oil were obtained under the humidity factor at medium levels and not at low or high levels. The analysis of the volatile fraction of the extracted fresh sample showed a content of 42 compounds in its composition, among them the carvacryl acetate, trans-caryophillene and germacrene D; while, the results of the stored sample essential oil showed a composition 24 compounds highlighting the presence of trans-Caryophyllene and sabinene. These results are interesting for research and are potentially useful in the food and pharmacology industry.

Chemical Composition of Essential Oil in Mosla Chinensis Maxim Cv. Jiangxiangru and its Inhibitory Effect on Staphylococcus Aureus Biofilm Formation.

The essential oil of Mosla chinensis Maxim cv. Jiangxiangru is known for its antibacterial ability. This study aimed to investigate the chemical composition of Jiangxiangru essential oil and its inhibitory effect on Staphylococcus aureus biofilm formation. Gas chromatography/mass spectrometry (GC–MS) was used to determine the chemical composition of Jiangxiangru essential oil. Subsequently, the eight major chemical components were quantitatively analyzed using GC– MS, and their minimum inhibitory concentration (MIC) values against S. aureus were tested. Biofilm formation was detected by crystal violet semi-quantitative method and silver staining. Of the 59 peaks detected, 29 were identified by GC–MS. Of these peaks, thymol, carvacrol, p-cymene, γ-terpinene, thymol acetate, α-caryophyllene, 3-carene, and carvacryl acetate were present at a relatively higher concentration. The results of the quantitative test showed that thymol, carvacrol, p-cymene, and γ-terpinene were the major components of the essential oil. Among the eight reference substances, only thymol, carvacrol, and thymol acetate had lower MICs compared with the essential oil. Essential oil, carvacrol, carvacryl acetate, α-caryophyllene, and 3-carene showed the better inhibition of S. aureus biofilm formation. When one fourth of the MIC concentrations were used for these substances (0.0625 mg/mL for essential oil, 0.0305 mg/mL for carvacrol, 1.458 mg/mL for carvacryl acetate, 0.1268 mg/mL for α-caryophyllene, and 2.5975 mg/mL for 3-carene), the inhibition rates were over 80%. However, thymol, γ-terpinene, thymol acetate, and p-cymene showed a relatively poor inhibition of S. aureus biofilm formation. When 1× MIC concentrations of these substances were used, the inhibition rates were less than 50%. In conclusion, Jiangxiangru essential oil and its major components, carvacrol, carvacryl acetate, α-caryophyllene, and 3-carene, strongly inhibited biofilm formation in S. aureus.

α-Glucosidase Inhibition and Antibacterial Activity of Secondary Metabolites from the Ecuadorian Species Clinopodium taxifolium (Kunth) Govaerts.

The phytochemical investigation of both volatile and fixed metabolites of Clinopodium taxifolium (Kunth) Govaerts (Lamiaceae) was performed for the first time. It allowed the isolation and characterization of the essential oil and six known compounds: carvacrol (1), squalane (2), uvaol (3), erythrodiol (4), ursolic acid (5), and salvigenin (6). Their structures were identified and characterized by Nuclear Magnetic Resonance (NMR) and Gas Chromatography coupled to Mass Spectroscopy (GC-MS), and corroborated by literature. The essential oil of the leaves was obtained by hydrodistillation in two different periods and analyzed by GC-MS and GC coupled to Flame Ionization Detector (GC-FID). A total of 54 compounds were detected, of which 42 were identified (including trace constituents). The major constituents were carvacrol methyl ether (18.9–23.2%), carvacrol (13.8–16.3%) and, carvacryl acetate (11.4–4.8%). The antibacterial activities were determined as Minimum Inhibition Concentration (MIC) against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa and Micrococcus luteus. The hexane and methanol extracts exhibited activity only against Klebsiella pneumoniae (250 and 500 μg/mL respectively), while the ethyl acetate extract was inactive. The hypoglycemic activity was evaluated by the in vitro inhibition of α-glucosidase. The ethyl acetate (EtOAc) extract showed strong inhibitory activity with IC50 = 24.88 µg/mL, however methanolic and hexanic extracts showed weak activity. As a pure compound, only ursolic acid showed a strong inhibitory activity, with IC50 = 72.71 μM.

Carvacryl acetate, a novel semisynthetic monoterpene ester, binds to the TRPA1 receptor and is effective in attenuating irinotecan-induced intestinal mucositis in mice.

We aimed to determine whether carvacryl acetate acts as a TRPA1 receptor agonist and its effects against irinotecan (CPT-11) induced intestinal mucositis in mice. TRPA1 structure was obtained from a protein databank, and the 3D structure of carvacryl acetate was determined. Appropriate binding conformations were discovered via automatic docking simulations. To determine the effect of carvacryl acetate in vivo, mice were treated with either DMSO 2%, CPT-11, carvacryl acetate followed by CPT-11, or HC-030031, a TRPA1 antagonist, followed by carvacryl acetate. Jejunum samples were taken and structural, inflammatory and antioxidant parameters were studied. Eight amino acids residues in TRPA1 established stable interactions with carvacryl acetate, which led to pharmacological efficacy against CPT-11-induced intestinal mucositis via reduction of both neutropenia and bacteremia, increase in villi height and crypt depth, decrease in pro-inflammatory cytokines (interleukin-1β, keratinocyte chemoattractant and tumour necrosis factor-α) and decrease in malondialdehyde and nitric oxide metabolite levels in the jejunum. Carvacryl acetate is a promising anti-inflammatory and antioxidant agent, a fact confirmed through observations of its interactions with TRPA1 in CPT-11-induced intestinal mucositis in mice.

Comparative efficacy and toxic effects of carvacryl acetate and carvacrol on sheep gastrointestinal nematodes and mice

Carvacrol is a compound isolated from some essential oils. It has been reported to possess anthelmintic activity. Acetylation of this monoterpene has been proposed as a potential way to reduce the toxicity and enhance the pharmacological effects of carvacrol. This study aimed to evaluate the effect of carvacryl acetate (CA) using in vitro and in vivo assays with gastrointestinal nematodes of small ruminants. The egg hatching test (EHT), larval development test (LDT) and adult worm motility (AWM) assessment were conducted to evaluate the effect of the acetylated product and pure carvacrol on Haemonchus contortus eggs, larvae and adults. The structural changes induced in adult H. contortus were assessed using scanning electron microscopy (SEM). CA and carvacrol acute toxicity was evaluated in mice. Finally, the efficacy of 250mg/kg CA and 2.5mg/kg monepantel (positive control) were evaluated in 30 sheep naturally infected with gastrointestinal nematodes by the fecal egg count reduction test (FECRT). In vitro tests were analyzed by analysis of variance (ANOVA) followed by comparison with Tukey’s test. The efficacy was calculated by the Boot Street program using the arithmetic average. The number of eggs in feces (epg) of the groups were transformed to log (x+1) and subjected to ANOVA to compare differences among the groups by Tukey’s test. The level of significance was P<0.05. CA and carvacrol inhibited larval hatching by 89.3 and 97.7% at doses of 8.0 and 1.0mg/ml, respectively. At the concentration of 2mg/ml, CA and carvacrol inhibited 100% of larval development. At a concentration of 200μg/ml, CA and carvacrol inhibited the motility of adult worms by 100% and 58.3% at 24h post-exposure, respectively. CA caused cuticle and vulvar flap wrinkling and bubbles to emerge from the tegument. Carvacrol caused more discreet effects on the cuticle and vulvar flap. The LD10 and LD50 of CA were 566.7mg/kg and 1544.5mg/kg, respectively. The LD10 and LD50 of carvacrol were 546.8mg/kg and 919mg/kg, respectively. CA and monepantel reduced the epg of sheep by 65.9 and 96.4%, respectively, at 16 days post-treatment. CA showed in vitro and in vivo anthelmintic activity and was less toxic than carvacrol.